Australian Herpes Management Forum

Reducing the Sexual Transmission of Genital Herpes

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Compiled by the Board of the Australian Herpes Management Forum (AHMF)

Introduction

People diagnosed with genital herpes usually have many questions and concerns, a key one being anxiety about possible transmission of the infection to a partner. Similarly, an infected partner is often anxious about the possibility of acquiring genital herpes from the infected person.

The Epidemiology of Genital Herpes

Genital herpes is one of the most common sexually transmitted infections worldwide. However, many individuals with this infection are asymptomatic or have minor symptoms that are not recognised by the patient or their health care provider as being due to herpes^1,2.

Genital herpes may be caused by either HSV-1 or HSV-2. A recent Australian study showed that 12% of Australian adults are infected with HSV-2, and 76% are infected with HSV-1. The study showed that HSV-2 infection is of public health importance within Australia as it is one of the commonest causes of genital ulceration and also implicated as an important co-factor for HIV transmission³. In the USA approximately one-fifth of the general population is HSV-2 seropositive⁵.

Another Australian study in women attending an antenatal clinic in western Sydney showed that HSV-2 prevalence was about 12%⁶. Not surprisingly, studies in patients attending sexual health clinics show a much higher prevalence (35-65%)^7,8. Other studies have reported high rates of infection in homosexual men, with HIV infected men having nearly twice the prevalence of HSV-2 than HIV negative men (61% vs 28%)⁹. A study conducted in NSW correctional centres reported a 58% seroprevalence rate in women versus 21% for males¹⁰.

Risk Factors Associated with HSV-2 Infection

A number of risk factors and behaviours are associated with HSV-2 infection (seropositivity). An understanding of these factors is important for the diagnosis of infection as well as discussion of possible interventions with patients to prevent or reduce HSV-2 transmission and acquisition.

Some of the more important risk factors associated with HSV-2 seropositivity include:

• Female gender: HSV-2 seropositivity is higher among women than men;
• Higher number of lifetime sexual partners: the risk of HSV-2 infection increases with the number of partners;
• Early age at first intercourse: this is likely to be a marker of longer duration of sexual activity and, therefore, exposure;
• Lower socio-economic status or level of education;
• History of a sexually transmitted disease: this is a marker of having partners who are at higher risk of HSV-2 infection; and,
• Age: HSV-2 seroprevalence increases with age, which likely reflects the cumulative increase in the number of sexual partners and the chronic nature of HSV-2 infection^11,12

Contributors to the Spread of Genital Herpes

Several factors may contribute to the epidemic spread of HSV-2 infection:

• Unrecognised infection and undiagnosed infection;
• Asymptomatic reactivation of the virus in individuals who are diagnosed with the infection and know they have the virus and also those with undiagnosed infection that are unaware they have the virus;
• Failure to use condoms; and
• Relatively low levels of treatment when genital herpes is diagnosed.

Facts about HSV transmission

• Genital HSV infection is transmitted by close physical (skin to skin) contact where the susceptible individual is exposed to the infectious virus from oral (usually HSV-1 associated with ‘cold sores’) or genital skin or mucosal surfaces. Such contact can be genital to genital or mouth to genital contact.
• HSV is readily transmitted when blisters or ulcers are present. However, the infection is more commonly transmitted through asymptomatic viral shedding (virus shedding without detectable lesions). Asymptomatic HSV shedding is common.
• Transmission commonly occurs from partners who are unaware that they are infected (i.e. they have unrecognised or asymptomatic genital HSV infection).
• Condoms consistently provide considerable prevention against sexual transmission of herpes for both men and women¹⁴.

Transmission of HSV-1 and HSV-2 often occurs from unrecognised symptomatic episodes or asymptomatic reactivations.

Reducing Transmission of HSV-2

A number of strategies have been suggested for reducing the risk of transmission of genital herpes.

Counselling and Education

Many patients with genital herpes are concerned about transmission, specifically who gave it to them and whether they have passed it on to anybody else. It is important for the health care provider to explain how transmission can occur, including the important issue of asymptomatic viral shedding. The AHMF has a clinical guideline on counselling and communication skills for people with genital herpes.

Some key counselling points that should be covered include:

• Genital herpes can be transmitted by genital to genital contact, genital to mouth contact or other skin contact with the genital area;
• Nearly everyone with genital herpes sheds the virus intermittently without symptoms and sexual transmission can occur during these periods;
• Sexual partners of infected persons should be advised that they might be infected even if they have no symptoms;
• Transmission of herpes can occur within monogamous long-term relationships;
• Transmission can occur in people who have never had penetrative sex, through close genital contact or oral genital contact;
• Asymptomatic viral shedding is more frequent in genital HSV-2 infection than genital HSV-1 infection and is most frequent in the first 12 months of acquiring HSV-2;
• Asymptomatic viral shedding may occur more frequently in immunocompromised individuals.

Condoms

Condoms are made of latex or polyurethane. There are 2 major types of condoms, those used by males and those used by females. Condoms act as a mechanical barrier to the spread of HSV. In vitro models have shown that male condoms are impermeable to HSV-2 and these studies confirm the effective nature of the mechanical barrier. Consequently, if condoms were able to cover all the affected anatomical areas and were used throughout every act of sexual contact they would provide excellent protection against transmission.

In reality the situation is somewhat different. First, condoms don’t cover all the affected sites and second, many couples don’t use condoms or use them intermittently. Nonetheless, a study involving 528 monogamous couples who were serodiscordant for HSV-2 showed that if condoms were used by infected males for at least 25% of sexual acts the risk of transmission to their female sexual partners was reduced by about 75%¹³. It is likely that more consistent condom usage would result in even greater reductions. The efficacy of female condoms to reduce HSV transmission during intercourse has not been assessed.

Antiviral Therapy andHSV Shedding

Patients with recurrent genital herpes can be treated with antiviral drugs. These drugs can be used intermittently (to treat each episode) or continuously (to prevent episodes)¹¹. Episodic therapy will decrease viral shedding during the treatment period, however will not affect asymptomatic viral shedding outside this time. Suppressive treatment is effective in suppressing recurrences and reducing symptomatic and asymptomatic shedding of HSV¹².

Aciclovir, famciclovir and valaciclovir all suppress symptomatic and asymptomatic viral shedding. These drugs have been shown in clinical trials to reduce asymptomatic HSV shedding by about 80-90%^14,15,16.

Antiviral Therapy and HSV Transmission

Antiviral therapy with valaciclovir has been shown to be effective in reducing the sexual transmission of HSV-2. This was demonstrated in the results of a randomised, placebo-controlled and double-blind trial of 1,500 couples with a history of less than 10 recurrences.

In the study the uninfected partners (or HSV-2 seronegative susceptible partners), who could be HSV-1 seropositive, were monitored monthly for acquisition of genital herpes. Couples were offered condoms and counselled on safe sexual behaviour at all visits.

Valaciclovir reduced the risk of transmission of clinical disease by 75% in the susceptible partner and the acquisition of genital HSV-2 infection (as assessed by serology) was reduced by 48%.

Once-daily valaciclovir suppressive therapy has been shown to significantly reduce the rate of acquisition of symptomatic HSV-2 infection.

Valaciclovir suppression is a useful component in the prevention of HSV-2 transmission and is probably best used in conjunction with condoms. The AHMF recommends that clinicians consider offering HSV-2 discordant couples once-daily suppressive therapy with valaciclovir as a useful adjunct to counselling on the use of condoms for the prevention of genital herpes transmission.

Management Strategies to Prevent Transmission

• Condoms may be partially effective in preventing acquisition of HSV.
• Suppressive antiviral therapy reduces asymptomatic shedding of HSV and clinical recurrences.
• Suppressive antiviral therapy with valaciclovir reduces the rate of acquisition of HSV-2 infection and clinically symptomatic genital herpes. Other antivirals may be effective, but efficacy has not been proven in clinical trials.

References

1. Corey L, Adams HG, Brown ZA, et al. Genital herpes simplex virus infections: Clinical manifestations, course, and complications. Annals of Internal Medicine 1983;98(6):958-972.
2. Wald A, Zeh J, Selke S, et al. Virologic characteristics of subclinical and symptomatic genital herpes infections. New England Journal of Medicine 1995;333(12):770-775.
3. Corey L. First-episode, recurrent, and asymptomatic herpes simplex infections. Journal of the American Academy of Dermatology 1988;18(1 Pt 2):169-172.
4. Smith JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: A global review. Journal of Infectious Diseases 2002;186 Supplementary 1:S3-28.
5. Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. New England Journal of Medicine 1997;337(16):1105-1111.
6. Tideman RL, Taylor J, Marks C, et al. Sexual and demographic risk factors for herpes simplex type 1 and 2 in women attending an antenatal clinic. Sexually Transmitted Infections 2001;77(6):413-415.
7. Cunningham AL, Lee FK, Ho DWT, et al. Herpes simplex virus type 2 antibody in patients attending antenatal or STD clinics 525-528. 1993 Medical Journal of Australia;158.
8. Bassett I, Donovan BJ, Bodsworth NJ, et al. Herpes simplex virus type 2 infection of heterosexual men attending a sexual health centre. The Medical Journal of Australia 1994;160:697-700.
9. Russell DB, Tabrizi SN, Russell JM, et al. Seroprevalence of herpes simplex virus types 1 and 2 in HIV-infected and uninfected homosexual men in a primary care setting. Journal of Clinical Virology 2001;22(3):305-313.
10. Butler T, Donovan B, Taylor J, et al. Herpes simplex virus type 2 in prisoners, New South Wales, Australia. International Journal of STD and AIDS 2000;11(11):743-747.
11. Cowan FM, Johnson AM, Ashley R, et al. Antibody to herpes simplex virus type 2 as serological marker of sexual lifestyle in populations. British Medical Journal 1994;309(6965):1325-1329.
12. Wald A, Koutsky L, Ashley RL, et al. Genital herpes in a primary care clinic: Demographic and sexual correlates of herpes simplex type 2 infections 149-155. 1997 Sexually Transmitted Diseases;24.
13. Wald A, Langenberg AG, Link K, et al. Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. Journal of the American Medical Association 2001;285(24):3100-3106.
14. Wald A, Barnum G, Selke S, et al. Acyclovir suppresses asymptomatic shedding of hsv-2 in the genital tract, 1994.
15. Reitano M, Tyring S, Lang W, et al. Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: A large-scale dose range-finding study. International valaciclovir HSV study group. Journal of Infectious Diseases 1998;178(3):603-610.
16. Schacker T, Hu HL, Koelle DM, et al. Famciclovir for the suppression of symptomatic and asymptomatic herpes simplex virus reactivation in HIV-infected persons. A double-blind, placebo-controlled trial. Annals of Internal Medicine 1998;128(1):21-28.
17. Corey L, Wald A, Patel R, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. New England Journal of Medicine 2004;350(1):11-20.

Disclaimer

The AHMF has made considerable efforts to ensure the information upon which this guideline is based reproduces the evidence as accurately as possible. Users of this guideline are strongly recommended to confirm that the information contained within them, especially drug indications, is correct by way of independent sources, as this guideline does not indicate an exclusive course of action or serve as a standard of medical care. The AHMF accepts no responsibility for any inaccuracies, information perceived as misleading, or the success of any treatment regimen detailed in this guideline.